The objectives of our studies are to investigate the immunological functions and molecular nature of alien H-2 specificities which we have detected on primary spontaneous and transplantable reticulum cell sarcoma (RCS) of SJL/J (H-25) mice. RCS has been shown to express public H-2K/O antigens which are cryptic on normal SJL/J cells by cellular, serological and immunochemical procedures. Furthermore, RCS express hybrid Ia antigens coded for by the Ia (Ae beta chain) and IE/C (E alpha chain) subregions which are not normally expressed on host SJL/J (H-25) cells but are present on lymphocytes of other haplotypes. In this investigation, we plan to define the molecular nature of the cross-reactive H-2 antigens using monospecific and monoclonal antibodies in order to determine if they are associated with the H-2K or D molecules. We will also define the biochemical nature of the hybrid IE/C antigen and its relationship to hybrid Ia of other H-2d and H-2k haplotypes. 1D and 2D PAGE will be done and supplemented by peptide mappings. The role of alien antigens of RCS in the stimulation of syngeneic lymphocytes will be examined by the use of various recombinant strains of F1 hybrids as responder and stimulator cells. The nature of stimulating antigens will be investigated by examining the effect of monoclonal antibodies on the proliferative response in vitro. Furthermore, the role of passive transfer of anti-alien antibodies on the in vivo tumor growth will be analyzed.